Thursday, February 10, 2005

The Recombinomics conundrum

On a number of occasions we have cited Henry Niman's Recombinomics site for important technical commentary regarding bird flu. Niman's views on a number of topics constitute one end of a spectrum of scientifically defensible positions. Because of the increasing visibility given his views (here and elsewhere), we would like to state our position regarding them as of this moment. None of the Effect Measure editors knows Niman personally or has spoken with him. We know him solely through the views expressed on his website.

Niman has staked out a position on several issues, maintaining:
  • that there is more evidence for person-to-person than WHO or the member governments (or Pro Med) imply. It seems to me that Niman's arguments are convincing for at least considering person-to-person transmission the default when familial or other close relation cases are separated from the index case by more than a week. His views on false negatives also seem plausible (example here). Advantage Niman.
  • that a variety of suspicious events (bird deaths in various places, example here; "meningo-like" disease in the Philippines) might be H5N1. This is clearly in the realm of speculation, and would not be credible were it not for the special context. While in most of these cases the facts will likely show them due to other causes, Niman's plea for an increase in the index of suspicion for H5N1 makes sense. Indeed I find the failure of authorities to confirm or disconfirm his suggestions publicly unfortunate because we don't know if they have even considered the possibility, and if not, why not. Advantage Niman.
  • that estimates of possible bird flu deaths in the event of a pandemic are much higher (1 billion) than WHO and many others predict. I consider the WHO 2 - 7 million death estimate a laughable low-ball figure. In an earlier post, commenting on the wide range of estimates, I showed how the number could even exceed Niman's estimates, given the right, and not implausible, assumptions. No one knows what the right figure is here. I think WHO is using figures that are an underestimate of the most probable number, given what we know. Unfortunately it is also the number most frequently quoted in the press. No one has the clear advantage here, but I think WHO's (and CDC's) low-ball strategy is indefensible.
  • that the importance of recombination versus reassortment in generating genetic variation in influenza has been overlooked. This is difficult to evaluate as Niman is principal of a commercial enterprise (Recombinomics) whose rationale is that recombination is the most important generator of diversity in viruses and that there are rules that can anticipate it and lead to useful products and interventions. He has stated this proposition as pertinent to H5N1 (and I posted on it earlier, here). It is important because currently the emphasis is on reassortment and recombination is not being scrutinized, possibly missing an important signal. However the scientific issues are somewhat controversial, in my reading, as negative-sense RNA viruses (like influenza) do not seem to exhibit much recombination, at least according to some measures. Whether this is also true specifically of the influenza A negative sense RNA virus is less clear, with mixed indications for different measures of recombination. The poster child for recombination would seem to be the 1918 flu, but its origins are still unclear, and the role of recombination has been disputed. I'd call this a legitimate draw. The jury is still out on this one.
  • The existence of WSN/33 human genes in swine sequences (see an example of one of Niman's posts here) is also difficult to assess, as Niman has not published his work to my knowledge. These genes, from a virulent and neurotropic strain isolated in 1933, should not be in Korean swine, where Niman says he detected them in sequences deposited in GenBank last fall. He suggests they could have gotten there by a lab accident or contamination, by accidental release from a military facility experimenting with the virus as a weapon, or as a bioterrorist incident. He has reported his findings to WHO and he writes that FAO is confirming, but to date says he has not had a response. Again, this is an instance where some public notification from the international agencies, one way or another (or even to say they are still evaluating it), should be the least to expect. While the jury is hence still out on this, some response from WHO or FAO seems appropriate. I consider Niman's scenarios unlikely and cannot vouch for the accuracy of the sequences, but silence on the part of the agencies seems like the wrong way to handle this. Full disclosure of whatever they know is indicated.
In summary, Niman may turn out wrong in some or all of the positions he has pushed on his site, but I find his general approach more defensible and appropriate given the stakes involved.